ArticleProceedings of the National Academy of Sciences of the United States of America2010
The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 74 citations in OpenAlex.
- Bacterial biosynthetic superclusters: emerging drivers of synergistic natural products against antimicrobial resistance.Essays in biochemistry · 2026Review
- Structure of a barrel-stave pore formed by magainin-2 reveals anion selectivity and zipper-mediated assembly.Scientific reports · 2025Article
- Rare distribution of butenolide-type signaling molecules among Streptomyces strains and functional importance as inducing factors for secondary metabolite production in Streptomyces rochei 7434AN4.The Journal of antibiotics · 2025Article
- 2-Amino-3-Chlorobenzoic Acid fromPharmaceuticals (Basel, Switzerland) · 2025Article
- Discovery of antimalarial drugs from secondary metabolites in actinomycetes culture library.Tropical medicine and health · 2024Article
- Description and genomic characterization of Cohnella caldifontis sp. nov., isolated from hot springs in Yunnan province, south-west China.Antonie van Leeuwenhoek · 2024Article
- Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A.Nature communications · 2023Article
- Identification and Characterization of a Potential Antibiotic Producing Strain ofJournal of genomics · 2022Article
- Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria.Nature microbiology · 2021Review
- Modular Chemical Synthesis of Streptogramin and Lankacidin Antibiotics.Accounts of chemical research · 2021Article
- Minimal biophysical model of combined antibiotic action.PLoS computational biology · 2021Article
- Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin inFrontiers in microbiology · 2021Article
- Modular Approaches to Lankacidin Antibiotics.Journal of the American Chemical Society · 2020Article
- Functional Analysis of P450 Monooxygenase SrrO in the Biosynthesis of Butenolide-Type Signaling Molecules inBiomolecules · 2020Article
- Computational Prediction of the Mode of Binding of Antitumor Lankacidin C to Tubulin.ACS omega · 2019Article
- Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.Annual review of biochemistry · 2018Review
- Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops.Biochemistry · 2018Article
- Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition Activity Toward Multi-Drug Resistant Bacterial Pathogens.Frontiers in microbiology · 2018Article
- Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action.Cellular and molecular life sciences : CMLS · 2016Review
- Ribosomal Antibiotics: Contemporary Challenges.Antibiotics (Basel, Switzerland) · 2016Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.